Malaysian Applied Biology Journal

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46_04_06

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Malays. Appl. Biol. (2017) 46(4): 43–53

GLYCOGEN SYNTHASE KINASE-3 Beta (GSK Beta) AS A MOLECULAR

TARGET FOR CYTOKINE-MODULATING EFFECT OF

CURCUMIN IN A MURINE MODEL OF ACUTE

MELIOIDOSIS INFECTION

 

ANDERSON TAN, NAGESSWARY GANESAN, SUHAINI SUDI, SOK KUAN WONG,

NOOR EMBI and HASIDAH MOHD SIDEK*


School of Biosciences and Biotechnology, Faculty of Science and Technology,

Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan, Malaysia.

 

*Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Accepted 27 November 2017, Published online 31 December 2017

 

ABSTRACT

The present study was conducted to investigate the effect of curcumin treatment on survivability, cytokine response, and phosphorylation of glycogen synthase kinase-3? (GSK3?) in Burkholderia pseudomallei-infected mice. Curcumin, a bioactive compound identified in Curcuma longa has been reported to exhibit anti-inflammatory properties via inactivation of nuclear factor-kappa B (NF-?B) and consequent downregulation of pro-inflammatory cytokine production. Glycogen synthase kinase- 3? (GSK3?) plays a pivotal role in the regulation of cytokine production. Here we used a murine model of acute melioidosis to investigate the effects of curcumin administration on experimental animal survivability, the phosphorylation state of GSK3? and levels of tumor necrosis factor (TNF)-?, interferon (IFN)-? and interleukin (IL)-10 in serum, liver and spleen of B. pseudomallei-infected mice. Intraperitoneal administration of curcumin (60 mg/kg b.w.) significantly (P<0.05) improved survivability (44%) of infected mice compared to non-treated controls. Administration of curcumin resulted in elevated phosphorylation of Ser9 GSK3? (pGSK3?) levels in both liver and spleen of B. pseudomallei-infected mice (1.2-2.6 fold) compared to non-treated infected controls. In addition, curcumin treatment significantly (P<0.05) decreased (30% - 85%) the levels of pro-inflammatory cytokines (TNF-? and IFN-?) in liver, spleen and serum of mice challenged with B. pseudomallei compared to non-treated infected controls. Increased levels (67%) of anti-inflammatory cytokine (IL-10) was also observed in serum of curcumin-treated infected mice. Our findings demonstrated that curcumin improved survivability of mice experimentally-infected with B. pseudomallei by modulating the pro- and anti-inflammatory cytokine response via inhibition of GSK3?.

Key words: Burkholderia pseudomallei, curcumin, glycogen synthase kinase-3?

 

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